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Stage III/IV MelanomaPhase 2Keynote-695NCT03132675

Tavo and Pembrolizumab in Patients With Stage III/IV Melanoma Progressing on Either Pembrolizumab or Nivolumab Treatment

A Phase 2 study testing tavokinogene telseplasmid, Pembrolizumab and ImmunoPulse in people with Stage III/IV Melanoma, run by OncoSec Medical Incorporated at 33 sites in 5 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

Keynote 695 is Phase 2 study of intratumoral tavokinogene telseplasmid (tavo; pIL-12) Electroporation (EP) plus IV Pembrolizumab. Eligible patients will be those with pathological diagnosis of unresectable or metastatic melanoma who are progressing or have progressed on either pembrolizumab or nivolumab. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Stage III/IV Melanoma
What is being tested?
tavokinogene telseplasmid, Pembrolizumab and ImmunoPulse
Could I receive a placebo?
No, everyone receives an active treatment
How many people
143 participants
Where
33 sitesin 5 countries
Study dates
3 Oct 2017to 31 Jul 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • In order to be eligible for participation in this study, the subject must meet all of the following:
  • All Cohorts:
  • Pathologically documented unresectable melanoma, American Joint Committee on Cancer (AJCC) version 8, Stage III or IV. Subjects must have histological or cytological confirmed diagnosis of unresectable melanoma with progressive locally advanced or metastatic disease.
  • Subjects must be refractory to anti-PD-1 monoclonal antibodies (mAb) (pembrolizumab or nivolumab either as monotherapy or in combination with other approved checkpoint inhibitors or targeted therapies according to their approved label) and subjects must meet all of the following criteria:
  • Received treatment of FDA-approved anti-PD1 mAb (dosed per label of the country providing the clinical site) for at least 12 weeks (eg, 4 administrations of q3w 200 mg pembrolizumab or 2 administrations of q6w 400 mg pembrolizumab).
  • Progressive disease after anti-PD-1 mAb will be defined according to RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment, no less than 4 weeks from the date of the first documented PD, in the absence of rapid clinical progression. For cases of rapid clinical progression, patients may be allowed to enroll without a confirmatory scan after discussion with the sponsor. (This determination is made by the Investigator; the Sponsor will collect imaging scans for retrospective analysis. Once PD is confirmed, the initial date of PD documentation will be considered the date of disease progression).
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  • Documented disease progression within 12 weeks of the last dose of anti- PD-1 mAb. Subjects who were re-treated with anti-PD-1 mAb and subjects who were on maintenance with anti-PD-1 mAb will be allowed to enter the study as long as there is documented PD within 12 weeks of the last treatment date (with anti-PD-1 mAb).
  • Note: anti-PD-1 combination therapy is acceptable as the last prior treatment and may include, anti-PD-1 anti-CTLA4 antibody combination therapy and anti-PD-1 combinations with investigational or injectable therapy.
  • Cohort 2:
  • Subjects must have received ipilimumab alone or in combination with nivolumab (or another agent) within approximately 12 months and must meet the following criteria:
  • Subject received 4 doses of ipilimumab (alone or in combination) or stopped treatment due to treatment-related adverse event, or investigator determined that the risks of further exposure outweigh the benefits.
  • Subjects with rapid clinical progression after fewer than 4 doses may be allowed after discussion with the sponsor.
  • All Cohorts:
  • Resolution/improvement of anti-PD-1 mAb related adverse events (including immune related AEs; irAEs) back to Grade 0-1 and ≤10 mg/day prednisone (or equivalent dose) for irAEs for at least 2 weeks prior to the first dose of study drug:
  • No history of common toxicity criteria adverse events (CTCAE) Grade 4 irAEs from anti-PD-1 mAb.
  • No history of CTCAE Grade 3 requiring steroid treatment (>10 mg/day prednisone or equivalent dose) for >12 weeks or CTCAE Grade 2 pneumonitis regardless of steroid treatment. No history of (non-infectious) pneumonitis or interstitial lung disease that required steroids, and no current pneumonitis or interstitial lung disease.
  • Minimum of 4 weeks (washout period) from the last dose of anti-PD-1 mAb
  • BRAF V600 mutation-positive melanoma could have received standard of care targeted therapy for advanced or metastatic disease (eg, BRAF/MEK inhibitor, alone or in combination) prior to enrolling on this study; however they do not need to have progressed on this treatment.
  • Age ≥ 18 years of age on day of signing informed consent.
  • Has a performance status of 0 or 1 on the ECOG Performance Scale, collected within 7 days of initial treatment.
  • Have measurable disease based on RECIST v1.1, with at least one anatomically distinct lesion. At least one lesion must meet all the following baseline criteria:
  • Accessible for electroporation;
  • Must be accurately measured in at least one dimension (longest diameter in the plane of measurement is to be recorded) Note: Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
  • Demonstrate adequate organ function. All screening laboratories should be performed within 10 days of treatment initiation.
  • Women of childbearing potential must have negative pregnancy test (for serum or urine pregnancy test, within 72 hours or 24 hours, respectively, prior to receiving the first study drug administration). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • For women of childbearing potential, must be willing to use an adequate method of contraception from the first day of study treatment (or 14 days prior to the initiation of study treatment for oral contraception) and through at least 120 days following last day of study treatment. Acceptable methods include hormonal contraception (oral contraceptives
  • as long as on stable dose, patch, implant, and injection), intrauterine devices, or double barrier methods (eg, vaginal diaphragm/ vaginal sponge plus condom, or condom plus spermicidal jelly), sexual abstinence or a vasectomized partner. Women may be surgically sterile or at least 1-year post-last menstrual period. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Note: Spermicide alone is not considered sufficient and will not be accepted
  • Male subjects must be surgically sterile or must agree to use adequate method of contraception when having sex with women of childbearing potential and refrains from sperm donation during the study treatment period and through at least 120 days following the last day of study drug administration.. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Able and willing to provide written informed consent and to follow study instructions.

Who cannot join

  • Subject has disease that is suitable for local therapy administered with curative intent.
  • Clinically active CNS metastases. Subjects with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study drug.
  • Subject with a diagnosis of uveal or mucosal melanoma.
  • Subject with clinically unstable or uncontrolled secondary malignancy that is progressing, or requires active treatment are excluded. In addition, subjects who have had a secondary malignancy that has resolved within the last 6 months, are also excluded.
  • Subject who had an allogenic tissue/solid organ transplant.
  • Subjects who have had intervening therapy following confirmed progression on anti-PD-1 therapy or anti-PD-1 combination therapy with the exception of BRAF inhibitors or BRAF/MEK inhibitor combinations.
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  • Note: anti-PD-1 combination therapy is acceptable as the last prior treatment and may include, anti-PD-1 anti-CTLA4 antibody combination therapy and anti-PD-1 combinations with investigational or injectable therapy.
  • Subjects who have received 4 or more lines of prior therapy, may be allowed to enroll after discussion with the Medical Monitor.
  • Subjects with electronic pacemakers or defibrillators.
  • Subjects who have a known history of Human Immunodeficiency Virus (HIV) (HIV1/2 antibodies). HIV-infected subjects with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
  • Subjects who have a known history of Hepatitis B or C infections or known to be positive for Hepatitis B antigen (HBsAg) or Hepatitis B virus (HBV) DNA or active. Active Hepatitis C. Active Hep C is defined by a known positive Hep C Ab result and known quantitative HCV RNA results greater than the lower limits of detection of the assay
  • Subject has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
  • Subjects who have received a live-virus or live-attenuated vaccination within 30 days of the first dose of treatment. Note: Administration of killed vaccines are allowed. Seasonal flu and COVID-19 vaccines that do not contain live virus are permitted.
  • Subject has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  • Subject has a history of (non infectious) pneumonitis or interstitial lung disease that required steroids or has current pneumonitis or interstitial lung disease.
  • Subject has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
  • Subject has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent, excluding thyroid, hypo adrenal, and diabetes if well controlled.
  • Note: Subjects with ≤Grade 2 neuropathy or ≤Grade 2 alopecia and hypopigmentation are an exception to this criterion and may qualify for the study.
  • Note: Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible if approved by the Sponsor.
  • Note: If subject underwent major surgery or radiation therapy of >30 Gy within 2 weeks of enrollment, they must have recovered adequately from the procedure and/or any complications from the intervention prior to starting study combination therapy.
  • Participation in another clinical study of an investigational anti-cancer agent or has used an investigational device within 30 days of screening.
  • Note: Subjects participating in an observational or supportive care study are an exception to this criterion and may qualify for the study with Sponsor approval.
  • Note: Subjects who have entered the follow up phase of an investigational study may participate as long as it has been 30 days after the last dose of the previous investigational agent.
  • Subject has known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study.
  • Subjects who are pregnant or breast-feeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.

Trial locations and contacts

33 sites in 5 countries.

33 sites in 5 countries

United States23 sites

  • University of Michigan, Michigan Medicine Melanoma Oncology Clinic - Rogel Cancer Center

    Ann Arbor, Michigan, 48109

  • University of Colorado Anschutz Medical Campus University of Colorado Cancer Center

    Aurora, Colorado, 80045

  • St. Luke's University Health Network

    Bethlehem, Pennsylvania, 18015

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Gabrail Cancer Center

    Canton, Ohio, 44718

  • Texas Oncology/Baylor

    Dallas, Texas, 75246

  • Duke University

    Durham, North Carolina, 27710

  • Penn State Health Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • Houston Methodist Cancer Center

    Houston, Texas, 77030

  • University of California, San Diego

    La Jolla, California, 92093

  • Dartmouth Hitchcock Clinic

    Lebanon, New Hampshire, 03756

  • University of Miami Sylvester Cancer Center

    Miami, Florida, 33136

  • Atlantic Health System

    Morristown, New Jersey, 07860

  • Ochsner Cancer Institute

    New Orleans, Louisiana, 70121

  • UF Health Cancer Center at Orlando Health

    Orlando, Florida, 32806

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Health Quest Systems, Inc.

    Poughkeepsie, New York, 12601

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84107

  • UCSF Medical Center

    San Francisco, California, 94115

  • Moffit Cancer Center

    Tampa, Florida, 33612

  • The University of Arizona Cancer Center

    Tucson, Arizona, 85724

  • Yuma Regional Medical Center, Yuma Cancer Center

    Yuma, Arizona, 85364

Other trials in United States

Australia6 sites

  • Box Hill Hospital

    Box Hill, Victoria, 3128

  • Cavalry Central Districts Hospital

    Elizabeth Vale, South Australia, 5112

  • The Alfred Hospital

    Melbourne, Victoria, 3004

  • St John of God Hospital

    Subiaco, Western Australia, 6008

  • Westmead Hospital

    Westmead, New South Wales, 2145

  • Princess Alexandra Hospital

    Woolloongabba, Queensland, 4102

Other trials in Australia

Canada2 sites

  • McGill University Health Centre

    Montreal, Quebec, H4A 3J1

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G2M9

Other trials in Canada

Italy1 site

  • Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

    Naples, 80131

Other trials in Italy

Switzerland1 site

  • University of Zurich, Dermatology Clinic

    Zurich, Canton of Zurich

Other trials in Switzerland

About this study

Official title: A Multicenter Phase 2, Open Label Study of Intratumoral Tavokinogene Telseplasmid (Tavo, pIL-12) + Electroporation With Pembrolizumab in Patients With Stage 3/4 Melanoma Who Are Progressing on Either Pembrolizumab or Nivolumab Treatment

Keynote 695 is Phase 2 study of intratumoral tavokinogene telseplasmid (tavo; pIL-12) Electroporation (EP) plus IV Pembrolizumab. Eligible patients will be those with pathological diagnosis of unresectable or metastatic melanoma who are progressing or have progressed on either pembrolizumab or nivolumab.

Read the detailed description

The study will be comprised of a screening period, a treatment period (up to 2 years), a long term follow-up period, and a survival follow-up period.

Eligible subjects will be treated with TAVO-EP to the accessible lesions on days 1, 5, and 8 every 6 weeks and with IV pembrolizumab (200 mg) on Day 1 of each 3-week cycle for up to 18 TAVO-EP cycles and 35 pembrolizumab cycles (from baseline) of continued treatment (approximately 2 years) or until disease progression. As many accessible lesions may be treated, as deemed feasible by the treating physician, as long as the size of each lesion is greater than 0.3 cm × 0.3 cm.

Long-term Follow-up: All subjects will be followed after End of Treatment (EOT) visit for SAEs (through 90 days from last dose of study drug). Subjects who discontinue treatment will enter the long-term follow-up period unless they have started a new anti-cancer therapy (or other local anticancer immunotherapy) or have withdrawn consent for non-survival assessments. They will have scans, photographs, and investigator-assessed disease evaluation per RECIST v1.1 collected every 3 months until disease progression, or the subject receives a new systemic anti-cancer treatment (or other local anticancer immunotherapy).

Survival Follow-up: Once a subject receives a new systemic anti-cancer treatment (or other local anticancer immunotherapy), they will move into survival follow-up. All subjects will be followed for survival and disease status, every 3 months up to a total duration of 5 years, withdrawal of consent, or until Sponsor terminates the study.

Being tested
tavokinogene telseplasmid, Pembrolizumab, ImmunoPulse
Keywords
Melanoma, pIL-12, pembrolizumab, tavokinogene telseplasmid, Keynote 695, IL-12, IL12, plasmid interleukin-12
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • tavokinogene telseplasmidBiological

    Also called pIL-12, tavo-EP

    Intratumoral tavokinogene telseplasmid (tavo, pIL-12) delivered by electroporation every 6 weeks

  • PembrolizumabBiological

    Also called Keytruda

    Intravenous 3 weekly treatments

  • ImmunoPulseDevice

    Also called tavo-EP

    Device that electroporates the tavokinogene telseplasmid

Study groups in NCT03132675
Study groupRoleWhat they receive
tavo-EP plus IV pembrolizumabExperimentalIntratumoral Tavokinogene Telseplasmid (tavo, pIL 12) plus Electroporation (ImmunoPulse) in Combination with Intravenous Pembrolizumab
Receives: Biological: tavokinogene telseplasmid; Biological: Pembrolizumab; Device: ImmunoPulse

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR)

    ORR by blinded independent central review (BICR) based on RECIST v1.1

    Measured: approximately 2 years

Secondary outcomes (6)

  1. Objective Response rate (ORR)

    ORR by investigator assessment based on RECIST v1.1

    Measured: approximately 2 years

  2. Duration of Response (DOR)

    DOR by Investigator assessment and BICR based on RECIST v1.1

    Measured: approximately 2 years

  3. Progression free survival (PFS)

    PFS by investigator assessment and BICR based on RECIST v1.1

    Measured: approximately 2 years

  4. Immune Progression Free Survival (iPFS)

    iPFS by Investigator assessment and BICR based on iRECIST

    Measured: approximately 2 years

  5. Immune Overall Response Rate (iORR)

    iORR by Investigator assessment and BICR based on iRECIST

    Measured: approximately 2 years

  6. Overall survival (OS)

    Overall survival

    Measured: approximately 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Apr 2017
  2. Study start3 Oct 2017
  3. Primary completion31 Mar 2023 (estimated)
  4. Study completion31 Jul 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Cohort 1A\_Locally advanced/metastatic melanoma: pathological diagnosis of unresectable or metastatic melanoma with progression on pembrolizumab or nivolumab, confirmed according to RECIST v1.1. BRAF V600 mutation-positive melanoma could have received standard of care targeted therapy for advanced or metastatic disease (eg, BRAF/MEK inhibitor, alone or in combination) prior to enrolling on this study; however, progression is not required. Cohort 1B\_Locally advanced/metastatic melanoma: Subjects will be enrolled in order to collect safety data using the GenPulse generator. Eligibility for enrollment will be the same as that for Cohort 1A. Cohort 2\_Locally advanced/metastatic melanoma with prior exposure to ipilimumab alone or in combination with nivolumab (or other drug(s)/agent(s)): Eligible subjects will be those with pathological diagnosis of unresectable or metastatic melanoma who have been exposed to ipilimumab alone or in combination with nivolumab (or other drug/agent)
Masking
None (open label)
Enrolment
143 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03132675
Sponsor's protocol ID
OMS-I103 (KEYNOTE 695)
Other IDs
Keynote-695, MK3475-695
Acronym
Keynote-695
Status last verified
Mar 2023
First submitted
24 Apr 2017
Last updated
27 Mar 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
Yes: There is a DSMB charter that makes anonymised data available.

Publications

  • Jacobs L, Yshii L, Junius S, Geukens N, Liston A, Hollevoet K, Declerck P. Intratumoral DNA-based delivery of checkpoint-inhibiting antibodies and interleukin 12 triggers T cell infiltration and anti-tumor response. Cancer Gene Ther. 2022 Jul;29(7):984-992. doi: 10.1038/s41417-021-00403-8. Epub 2021 Nov 9.

    PubMed 34754076

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing tavokinogene telseplasmid, Pembrolizumab and ImmunoPulse in people with Stage III/IV Melanoma, run by OncoSec Medical Incorporated at 33 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 27 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in United States, Australia, Canada, Italy, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: approximately 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03132675, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2023.

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